By conjugating human albumin to agarose, affinity chromatrography columns have been developed which are highly effective in removing bilirubin from whole blood. Hemoperfusion of jaundiced rats for one hour with such columns has removed virtually the entire circulating bilirubin pool. Studies of this technique in jaundiced newborn monkeys have demonstrated a similar high degree of efficiency for removing bilirubin. These studies demonstrated an interesting species variation in the effects of hemoperfusion on formed element loss. Virtually no granulocytes or platelets were lost during hemoperfusion of rat blood through albumin-agarose but dramatic and clinically significant losses occurred in monkeys. Examination of the effects of calcium chelating agents and various prostaglandins on platelet and granulocyte losses during hemoperfusion have resulted in the development of techniques which completely abolish such losses during perfusion over a variety of sorbents including albumin-agarose gel, activated charcoal and neutral and charged synthetic resins. The focus of this study has now shifted to the development of a reproducible animal model of reversible fulminant hepatic failure. Such a model will be important in studying whether extracorporeal perfusion represents a rational approach to the treatment of fulminant hepatic failure in man.